Submissions for variant NM_001204.7(BMPR2):c.853-2A>G

gnomAD frequency: 0.00001  dbSNP: rs863223424

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000199603	SCV000249647	pathogenic	not provided	2015-06-04	criteria provided, single submitter	clinical testing	c.853-2 A>G:IVS6-2 A>G in intron 6 of the BMPR2 gene (NM_001204.6). The c.853-2 A>G mutation has been reported in at least one individual with idiopathic PAH (Machado R et al., 2006). This mutation destroys the canonical splice acceptor site in intron 6 and is predicted to cause abnormal gene splicing. The mutation is predicted to lead to an abnormal message that is subject to nonsense-mediated mRNA decay (Machado R et al., 2006). Other splice site mutations in the BMPR2 gene have been reported in association with PAH. Furthermore, the c.853-2 A>G mutation was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. In summary, c.853-2 A>G in the BMPR2 gene is interpreted as a disease-causing mutation. This variant was found in PAH-PANCARD
Center for Genomic Medicine, Kyoto University Graduate School of Medicine	RCV000242870	SCV000320708	pathogenic	Pulmonary hypertension, primary, 1	2016-07-11	no assertion criteria provided	clinical testing
Rare Disease Genomics Group, St George's University of London	RCV000242870	SCV000576118	pathogenic	Pulmonary hypertension, primary, 1		no assertion criteria provided	literature only
NIHR Bioresource Rare Diseases, University of Cambridge	RCV001003696	SCV001162139	likely pathogenic	Pulmonary arterial hypertension		no assertion criteria provided	research
Wendy Chung Laboratory, Columbia University Medical Center	RCV001823878	SCV002073606	not provided	Pulmonary arterial hypertension; Idiopathic and/or familial pulmonary arterial hypertension		no assertion provided	literature only